LMP7基因多态性与1型糖尿病易感性及DR3基因的关系

摘要

目的研究华南地区汉人大多功能蛋白酶(LMP)7基因与1型糖尿病(DM-1)易感性及DR3基因的关系。方法以聚合酶链反应-限制性片段长度多态性技术对71例DM-1患者及86例正常对照进行LMP7基因分型。根据DR3基因将DM-1患者及对照组分别分为DR3阳性组与DR3阴性组。分别于随机人群及DR3配对的人群比较LMP7各基因型及等位基因频率在DM-1患者与对照组之间的差异。根据发病年龄将DM-1分为3组，A组≤14岁，B组15-30岁，C组≥31岁。结果在随机人群：DM-1组LMP7-B/B频率显著降低(39% vs 58%，P<0.05)，LMP7-B/A频率显著升高(54% vs 31%，P<0.01)。在DR3阳性人群：LMP7各基因型及等位基因频率在DM-1组与对照组间无显著性差异。在DR3阴性人群：DM-1组LMP7-B/B频率显著降低(40% vs 61%，P<0.05)，LMP7-B/A频率显著升高(55% vs 28%，P<0.01)。 LMP各基因型及等位基因频率在糖尿病各发病年龄组间无显著性差异。结论 LMP7-B/B可能是DM-1的保护基因型， LMP7-B/A可能是DM-1的易感基因型，它们与DM-1的关系可能不受DR3基因的影响。LMP7-B/B基因型阳性者患DM-1危险性降低。LMP7-B/A基因阳性者患DM-1危险性增加。LMP7基因与DM-1发病年龄可能无关。%Objective To study the relationship of the large multifunctional proteasome 7 (LMP7) gene polymorphism with susceptibility to type 1 diabetes mellitus (DM-1) and the DR3 gene in south Chinese Han population.Methods LMP7 genotypes and the DR3 gene were identified in 71 DM-1 patients and 86 healthy persons (as controls) by polymerase chain reaction-restriction fragment length polymorphism. DM-1 patients and controls were divided into DR3-positive and DR3-negative subjects. The frequencies of LMP7 genotypes and alleles were compared between DM-1 patients and controls respectively in the random subjects and in the DR3-matched subjects. Furthermore, DM-1 patients were divided into 3 groups according to the age of diabetic onset: group A≤14 years, group B 15-30 years, group C≥31 years.Results In the random subjects, the frequency of LMP7-B/B was lower (39% vs 58%, P<0.05) and that of LMP7-B/A was higher (54% vs 31%, P<0.01) in DM-1 patients than that in controls. In DR3-positive subjects, the frequencies of LMP7 genotypes and alleles showed no differences between DM-1 patients and controls. In DR3-negative subjects, the frequency of LMP7-B/B was decreased (40% vs 61%) and that of LMP7-B/A was increased (55% vs 28%, P<0.01) in DM-1 patients. The frequencies of LMP7 genotypes and alleles showed no significant differences among different ages of diabetic onset.Conclusions LMP7-B/B may be the protective genotype, and LMP7-B/A may be the susceptible genotype of DM-1, and this may not be affected by the DR3 gene. Persons with LMP7-B/B may have a decreased risk, and those with LMP7-B/A have an increased risk suffering from DM-1. The LMP7 gene may not be associated with the age of diabetic onset.